Covid-19 Sentry

Contents

• From Preprints
• From Clinical Trials
• From PubMed
• From Patent Search

From Preprints

• Agreement Test Between The Six Minutes Walking Test And Four Meter Gait Speed -
  Background/Objective: In the field of Physical Medicine and Rehabilitation, it is essential to measure individual functional capacity, which could be evaluated through walking tests. Aside from the commonly used six minutes walking test (6MWT), four meter gait speed (4MGS) are widely used for its practicality. This study aimed to assess the agreement between 4 MGS and the 6MWT in Indonesian healthy adults. Methods: This agreement analysis study had recruited 61 healthy and sedentary Indonesians aged 18 until 50 years old, and they were instructed to perform three tests, namely 6MWT and 4MGS with six meters and eight meters track. These gait speed were then compared to assess validity. Results: Mean gait speed results for males in 6MWT is 1.602 m/s, whereas 4MGS in six meter track is 2.114 m/s and similarly 2.108 m/s in the eight meter track. Females on the other hand, achieved 1.462 m/s for 6MWT, 1.908 m/s and 1.986 m/s for 4MGS in six and eight meter simultaneously. Bland Altman Agreement test between the 6MWT and 4MGS shows scatter dots with close limit of agreement, thus showing a good agreement between the 6MWT and 4 MGS with both tracks. Discussion: Both track length of 4 MGS were in a good agreement with 6MWT for functional capacity assessment. Conclusions: In response to the COVID-19 pandemic era, shorter track of 4MGS (six meters) can be feasibly utilized. It is evident that shorter duration and track will boost the tests practicality in assessing functional capacity for both inpatient and outpatient settings.
  🖺 Full Text HTML: Agreement Test Between The Six Minutes Walking Test And Four Meter Gait Speed
• Median/modal death ages of pooled European male cohorts were near-constant for ~25/30 years. -
  Background. Longevity is of considerable interest. Collation of recent data after World War II by the Human Mortality Database allowed analyses, previously unattainable, of modal death-ages for sufficient numbers of large European pooled cohorts. Objective. To track modes, means and medians (>=60 years old (y)) of all-cause mortality for both sexes. Methods. The only highest-quality, large-number Lexis data available were pooled from nine European countries: Denmark, Finland, France, Iceland, Italy, Netherlands, Norway, Sweden and Switzerland; raw-data modes (and means/medians >=60y, plus thin-plate-splines), were analyzed, plus loess-smoothed equivalents for individual countries. Results. Here we show that for ~25-30 years (cohorts 1880-~1909) dramatic overall sex differences existed between pooled raw-death-age changes: male modal ages being near-constant (77.2y + standard deviation 1.58y); females’ increased. Overall, for available cohorts (1880-1904) male raw medians were exactly constant (76y); male means showed slight increase (0.0193y/year; compare female: 0.146y/year). Male deaths >=60<=76y compared with >76y, as percentages of total, were near-equal, whereas in females the former decreased. Only after ~1910 did male modal ages rapidly increase (other averages not calculable). Individual country results showed that males in Finland, France, Switzerland were affected less than other countries. Conclusions. Results clarify previously knowledge concerning sex differences during this period. Despite improved environment during late adulthood, this did not translate into increased male longevity and earlier events might have sealed their fate, especially in Denmark, Italy, Netherlands, Norway, and Sweden. One hypothesis concerns long-term effects of the 1918-1919 influenza pandemic, perhaps directly relevant to the Covid-19 pandemic at present.
  🖺 Full Text HTML: Median/modal death ages of pooled European male cohorts were near-constant for ~25/30 years.
• Preclinical Mesenchymal Stromal Cell Delivery Via An Ex Vivo Bioreactor Attenuates Clot Formation For Intravascular Applications -
  While mesenchymal stromal cells (MSCs) are an appealing therapeutic option for a range of clinical applications, their potential to induce clotting when used systemically remains a safety concern, particularly in hypercoagulable conditions, such as in patients with severe COVID-19, trauma, or cancers. Here, we tested a novel ex vivo approach aimed at improving the safety of MSC systemic administration by use of a bioreactor. In this device, MSCs are seeded on the outside of a hollow-fiber filter, sequestering them behind a hemocompatible membrane, while still maintaining cross talk with blood cells and circulating signaling molecules. The potential for these bioreactor MSCs to induce clots in coagulable plasma was compared against free MSCs, as a model of systemic administration, which were directly injected into the circuit. Our results showed that physical isolation of the MSCs via a bioreactor extends the time necessary for clot formation to occur when compared to free MSCs. Measurement of cell surface data indicates the presence of known clot inducing factors, namely tissue factor and phosphatidylserine. Results also showed that recovering cells and flushing the bioreactor prior to use further prolonged clot formation time. Further, application of this technology in two in vivo models did not require additional heparin to maintain target ACT levels relative to the acellular device. Taken together, the use of hollow fiber filters to house MSCs, if adopted clinically, could offer a novel method to control systemic MSC exposure and prolong clot formation time.
  🖺 Full Text HTML: Preclinical Mesenchymal Stromal Cell Delivery Via An Ex Vivo Bioreactor Attenuates Clot Formation For Intravascular Applications
• Baseline Cardiometabolic Profiles and SARS-CoV-2 Infection in the UK Biobank -

  Abstract Background SARS-CoV-2 is a rapidly spreading coronavirus with a high incidence of severe upper respiratory infection that first presented in Wuhan, China in December 2019. Many factors have been identified as risk factors for SARS-CoV-2, with much attention being paid to body mass index (BMI). Little investigation has been done to investigate dysregulation of lipid profiles and diabetes, which are often comorbid in high BMI patients. Objective This study seeks to describe the impact of BMI, HDL, LDL, ApoA, ApoB, triglycerides, hemoglobin A1c (HbA1c), diabetes, alcohol and red wine intake on the odds of testing positive for SARS-CoV-2 in UK Biobank (UKB) study participants. Methods We examined the effect of BMI, lipid profiles, diabetes and alcohol intake on the odds of testing positive for SARS-Cov-2 among 9,005 UKB participants tested for SARS-CoV-2 from March 16 through July 14, 2020. Odds ratios and 95% confidence intervals were computed using logistic regression adjusted for age, sex and ancestry. Results Higher BMI, Type II diabetes and HbA1c were associated with increased SARS-CoV-2 odds (p < 0.05) while HDL and ApoA were associated with decreased odds (p < 0.001). Though the effect of BMI, Type II diabetes and HbA1c were eliminated when HDL was controlled, the effect of HDL remained significant when BMI was controlled for. Additionally, red wine intake was associated with reduced odds of testing positive for SARS-CoV-2 (p < 0.05). LDL, ApoB and triglyceride levels were not found to be significantly associated with increased odds. Conclusion Elevated HDL and ApoA levels and alcohol intake, specifically red wine intake, were associated with reduced odds of testing positive for SARS-CoV-2, while higher BMI, type II diabetes and HbA1c were associated with increased odds. The effects of alcohol, BMI, type II diabetes and HbA1c levels were no longer significant after controlling for HDL, suggesting that these effects may be mediated in part through regulation of HDL levels. In summary, our study corroborates the emerging picture that high HDL levels may confer protection against SARS-CoV-2.

  🖺 Full Text HTML: Baseline Cardiometabolic Profiles and SARS-CoV-2 Infection in the UK Biobank
• AI-Driven Multiscale Simulations Illuminate Mechanisms of SARS-CoV-2 Spike Dynamics -
  We develop a generalizable AI-driven workflow that leverages heterogeneous HPC resources to explore the time-dependent dynamics of molecular systems. We use this workflow to investigate the mechanisms of infectivity of the SARS-CoV-2 spike protein, the main viral infection machinery. Our workflow enables more efficient investigation of spike dynamics in a variety of complex environments, including within a complete SARS-CoV-2 viral envelope simulation, which contains 305 million atoms and shows strong scaling on ORNL Summit using NAMD. We present several novel scientific discoveries, including the elucidation of the spike’s full glycan shield, the role of spike glycans in modulating the infectivity of the virus, and the characterization of the flexible interactions between the spike and the human ACE2 receptor. We also demonstrate how AI can accelerate conformational sampling across different systems and pave the way for the future application of such methods to additional studies in SARS-CoV-2 and other molecular systems.
  🖺 Full Text HTML: AI-Driven Multiscale Simulations Illuminate Mechanisms of SARS-CoV-2 Spike Dynamics
• A network modelling approach to assess non-pharmaceutical disease controls in a worker population: An application to SARS-CoV-2 -

  Background: As part of a concerted pandemic response to protect public health, businesses can enact non-pharmaceutical controls to minimise exposure to pathogens in workplaces and premises open to the public. Amendments to working practices can lead to the amount, duration and/or proximity of interactions being changed, ultimately altering the dynamics of disease spread. These modifications could be specific to the type of business being operated. Methods: We use a data-driven approach to parameterise an individual-based network model for transmission of SARS-CoV-2 amongst the working population, stratified into work sectors. The network is comprised of layered contacts to consider risk of spread in multiple encounter settings (workplaces, households, social and other). We analyse several interventions targeted towards working practices: mandating a fraction of the population to work from home, using temporally asynchronous work patterns and introducing measures to create `COVID-secure9 workplaces. We also assess the general role of adherence to (or effectiveness of) isolation and test and trace measures and demonstrate the impact of all these interventions across a variety of relevant metrics. Results: The progress of the epidemic can be significantly hindered by instructing a significant proportion of the workforce to work from home. Furthermore, if required to be present at the workplace, asynchronous work patterns can help to reduce infections when compared with scenarios where all workers work on the same days, particularly for longer working weeks. When assessing COVID-secure workplace measures, we found that smaller work teams and a greater reduction in transmission risk led to a flatter temporal profile for both infections and the number of people isolating, and reduced the probability of large, long outbreaks. Finally, following isolation guidance and engaging with contact tracing alone is an effective tool to curb transmission, but is highly sensitive to adherence levels. Conclusions: In the absence of sufficient adherence to non-pharmaceutical interventions, our results indicate a high likelihood of SARS-CoV-2 spreading widely throughout a worker population. Given the heterogeneity of demographic attributes across worker roles, in addition to the individual nature of controls such as contact tracing, we demonstrate the utility of a network model approach to investigate workplace-targeted intervention strategies and the role of test, trace and isolation in tackling disease spread.

  🖺 Full Text HTML: A network modelling approach to assess non-pharmaceutical disease controls in a worker population: An application to SARS-CoV-2
• Association of County-Wide Mask Ordinances with Reductions in Daily CoVID-19 Incident Case Growth in a Midwestern Region Over 12 Weeks -

  Importance: This study assessed the longitudinal impact of new COVID-19 cases when a mask ordinance was implemented in 2 of a 5-county Midwestern U.S. metropolitan region over a 3-month period of time. Reduction in case growth was significant and reduced infection inequities by race and population density. Objective: The objective of this study was to assess the impact that a mandatory mask wearing requirement had on the rate of COVID-19 infections by comparing counties with a mandatory policy with those neighboring counties without a mandatory masking policy. Design: This was a quasi-experimental longitudinal study conducted over the period of June 12-September 25, 2020. Setting: This study was a population-based study. Data were abstracted from local health department reports of COVID-19 cases. Participants: Raw cases reported to the county health departments and abstracted for this study; census-level data were synthesized to address county-level population, income and race. Intervention(s) (for clinical trials) or Exposure(s) (for observational studies): The essential features of this intervention was an instituted mask mandate that occurred in St. Louis City and St. Louis County over a 12 week period. Main Outcome(s) and Measure(s): The primary study outcome measurement was daily COVID-19 infection growth rate. The mask mandate was hypothesized to lower daily infection growth rate. Results: Over the 15-week period, the average daily percent growth of reported COVID-19 cases across all five counties was 1.81% (sd 1.62%). The average daily percent growth in incident COVID-19 cases was similar between M+ and M- counties in the 3 weeks prior to implementation of mandatory mask policies (0.90% [sd 0.68] vs. 1.27% [sd 1.23%], respectively, p=0.269). Crude modeling with a difference-in-difference indicator showed that after 3 weeks of mask mandate implementation, M+ counties had a daily percent COVID-19 growth rate that was 1.32 times lower, or a 32% decrease. At 12 weeks post-mask policy implementation, the average daily COVID-19 case growth among M- was 2.42% (sd 1.92), and was significantly higher than the average daily COVID case growth among M+ counties (1.36% (sd 0.96%)) (p<0.001). A significant negative association was identified among counties between percent growth of COVID-19 cases and percent racial minorities per county (p<0.001), as well as population density (p<0.001). Conclusions and Relevance: These data demonstrate that county-level mask mandates were associated with significantly lower incident COVID-19 case growth over time, compared to neighboring counties that did not implement a mask mandate. The results highlight the swiftness of how a mask ordinance can impact the trajectory of infection rate growth. Another notable finding was that following implementation of mask mandates, the disparity of infection rate by race and population density was no longer significant, suggesting that regional-level policies can not only slow the spread of COVID-19, but simultaneously create more equal environment.

  🖺 Full Text HTML: Association of County-Wide Mask Ordinances with Reductions in Daily CoVID-19 Incident Case Growth in a Midwestern Region Over 12 Weeks
• Anti-severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) potency of Mefloquine as an entry inhibitor in vitro -
  Coronavirus disease 2019 (COVID-19 ) has caused serious public health, social, and economic damage worldwide and effective drugs that prevent or cure COVID-19 are urgently needed. Approved drugs including Hydroxychloroquine, Remdesivir or Interferon were reported to inhibit the infection or propagation of severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2), however, their clinical efficacies have not yet been well demonstrated. To identify drugs with higher antiviral potency, we screened approved anti-parasitic/anti-protozoal drugs and identified an anti-malarial drug, Mefloquine, which showed the highest anti-SARS-CoV-2 activity among the tested compounds. Mefloquine showed higher anti-SARS-CoV-2 activity than Hydroxychloroquine in VeroE6/TMPRSS2 and Calu-3 cells, with IC50=1.28 M, IC90=2.31 M, and IC99=4.39 M in VeroE6/TMPRSS2 cells. Mefloquine inhibited viral entry after viral attachment to the target cell. Combined treatment with Mefloquine and Nelfinavir, a replication inhibitor, showed synergistic antiviral activity. Our mathematical modeling based on the drug concentration in the lung predicted that Mefloquine administration at a standard treatment dosage could decline viral dynamics in patients, reduce cumulative viral load to 7% and shorten the time until virus elimination by 6.1 days. These data cumulatively underscore Mefloquine as an anti-SARS-CoV-2 entry inhibitor.
  🖺 Full Text HTML: Anti-severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) potency of Mefloquine as an entry inhibitor in vitro
• Highly potent anti-SARS-CoV-2 multi-DARPin therapeutic candidates -
  Globally accessible preventive and therapeutic molecules against SARS-CoV-2 are urgently needed. DARPin molecules are an emerging class of novel therapeutics based on naturally occurring repeat proteins (about 15 kDa in size) and can be rapidly produced in bacteria in large quantities. Here, we report the identification of 380 DARPin molecules specifically targeting the SARS-CoV-2 spike protein selected from a naive library of 10^12 DARPin molecules. Using extensive biophysical and biochemical characterization, (pseudo)virus neutralization assays and cryo EM analysis, 11 mono-DARPin molecules targeting either the receptor binding domain (RBD), the S1 N-terminal-domain (NTD) or the S2 domain of the SARS-CoV-2 spike protein were chosen. Based on these 11 mono-DARPin molecules, 31 anti-SARS-CoV-2 multi-DARPin molecules were constructed which can broadly be grouped into 2 types; multi-paratopic RBD-neutralizing DARPin molecules and multi-mode DARPin molecules targeting simultaneously RBD, NTD and the S2 domain. Each of these multi-DARPin molecules acts by binding with 3 DARPin modules to the SARS-CoV-2 spike protein, leading to potent inhibition of SARS-CoV-2 infection down to 1 ng/ml (12 pM) and potentially providing protection against viral escape mutations. Additionally, 2 DARPin modules binding serum albumin, conferring an expected half-life of about 3 weeks in humans, were included in the multi-DARPin molecules. The protective efficacy of one multi-DARPin molecule was studied in a Golden Syrian hamster SARS-CoV-2 infection model, resulting in a significant reduction in viral load and pathogenesis. In conclusion, the multi-DARPin molecules reported here display very high antiviral potency, high-production yield, and a long systemic half-life, and thereby have the potential for single-dose use for prevention and treatment of COVID-19.
  🖺 Full Text HTML: Highly potent anti-SARS-CoV-2 multi-DARPin therapeutic candidates
• Unsupervised cluster analysis of SARS-CoV-2 genomes reflects its geographic progression and identifies distinct genetic subgroups of SARS-CoV-2 virus -
  Over 10,000 viral genome sequences of the SARS-CoV-2 virus have been made readily available during the ongoing coronavirus pandemic since the initial genome sequence of the virus was released on the open access Virological website early on January 11. We utilize the published data on the single stranded RNAs of 11,132 SARS-CoV-2 patients in the GISAID database, which contains fully or partially sequenced SARS-CoV-2 samples from laboratories around the world. Among many important research questions which are currently being investigated, one aspect pertains to the genetic characterization/classification of the virus. We analyze data on the nucleotide sequencing of the virus and geographic information of a subset of 7,640 SARS-CoV-2 patients without missing entries that are available in the GISAID database. Instead of modelling the mutation rate, applying phylogenetic tree approaches, etc., we here utilize a model-free clustering approach that compares the viruses at a genome-wide level. We apply principal component analysis to a similarity matrix that compares all pairs of these SARS-CoV-2 nucleotide sequences at all loci simultaneously, using the Jaccard index. Our analysis results of the SARS-CoV-2 genome data illustrates the geographic and chronological progression of the virus, starting from the first cases that were observed in China to the current wave of cases in Europe and North America. This is in line with a phylogenetic analysis which we use to contrast our results. We also observe that, based on their sequence data, the SARS-CoV-2 viruses cluster in distinct genetic subgroups. It is the subject of ongoing research to examine whether the genetic subgroup could be related to diseases outcome and its potential implications for vaccine development.
  🖺 Full Text HTML: Unsupervised cluster analysis of SARS-CoV-2 genomes reflects its geographic progression and identifies distinct genetic subgroups of SARS-CoV-2 virus
• Multiscale three-dimensional pathology findings of COVID-19 diseased lung using high-resolution cleared tissue microscopy -
  The study of pulmonary samples from individuals who have died as a direct result of COVID-19 infection is vital to our understanding of the pathogenesis of this disease. Histopathologic studies of lung tissue from autopsy of patients with COVID-19 specific mortality are only just emerging. All existing reports have relied on traditional 2-dimensional slide-based histological methods for specimen preparation. However, emerging methods for high-resolution, massively multiscale imaging of tissue microstructure using fluorescence labeling and tissue clearing methods enable the acquisition of tissue histology in 3-dimensions, that could open new insights into the nature of SARS-Cov-2 infection and COVID-19 disease processes. In this article, we present the first 3-dimensional images of lung autopsy tissues taken from a COVID-19 patient, including 3D “virtual histology” of cubic-millimeter volumes of the diseased lung, providing unique insights into disease processes contributing to mortality that could inform frontline treatment decisions.
  🖺 Full Text HTML: Multiscale three-dimensional pathology findings of COVID-19 diseased lung using high-resolution cleared tissue microscopy
• A network modelling approach to assess non-pharmaceutical disease controls in a worker population: An application to SARS-CoV-2 -

  Background: As part of a concerted pandemic response to protect public health, businesses can enact non-pharmaceutical controls to minimise exposure to pathogens in workplaces and premises open to the public. Amendments to working practices can lead to the amount, duration and/or proximity of interactions being changed, ultimately altering the dynamics of disease spread. These modifications could be specific to the type of business being operated. Methods: We use a data-driven approach to parameterise an individual-based network model for transmission of SARS-CoV-2 amongst the working population, stratified into work sectors. The network is comprised of layered contacts to consider risk of spread in multiple encounter settings (workplaces, households, social and other). We analyse several interventions targeted towards working practices: mandating a fraction of the population to work from home, using temporally asynchronous work patterns and introducing measures to create `COVID-secure9 workplaces. We also assess the general role of adherence to (or effectiveness of) isolation and test and trace measures and demonstrate the impact of all these interventions across a variety of relevant metrics. Results: The progress of the epidemic can be significantly hindered by instructing a significant proportion of the workforce to work from home. Furthermore, if required to be present at the workplace, asynchronous work patterns can help to reduce infections when compared with scenarios where all workers work on the same days, particularly for longer working weeks. When assessing COVID-secure workplace measures, we found that smaller work teams and a greater reduction in transmission risk led to a flatter temporal profile for both infections and the number of people isolating, and reduced the probability of large, long outbreaks. Finally, following isolation guidance and engaging with contact tracing alone is an effective tool to curb transmission, but is highly sensitive to adherence levels. Conclusions: In the absence of sufficient adherence to non-pharmaceutical interventions, our results indicate a high likelihood of SARS-CoV-2 spreading widely throughout a worker population. Given the heterogeneity of demographic attributes across worker roles, in addition to the individual nature of controls such as contact tracing, we demonstrate the utility of a network model approach to investigate workplace-targeted intervention strategies and the role of test, trace and isolation in tackling disease spread.

  🖺 Full Text HTML: A network modelling approach to assess non-pharmaceutical disease controls in a worker population: An application to SARS-CoV-2
• Meta-analysis of the SARS-CoV-2 serial interval and the impact of parameter uncertainty on the COVID-19 reproduction number -

  The serial interval of an infectious disease, commonly interpreted as the time between onset of symptoms in sequentially infected individuals within a chain of transmission, is a key epidemiological quantity involved in estimating the reproduction number. The serial interval is closely related to other key quantities, including the incubation period, the generation interval (the time between sequential infections) and time delays between infection and the observations associated with monitoring an outbreak such as confirmed cases, hospital admissions and deaths. Estimates of these quantities are often based on small data sets from early contact tracing and are subject to considerable uncertainty, which is especially true for early COVID-19 data. In this paper we estimate these key quantities in the context of COVID-19 for the UK, including a meta-analysis of early estimates of the serial interval. We estimate distributions for the serial interval with a mean 5.6 (95% CrI 5.1−6.2) and SD 4.2 (95% CrI 3.9−4.6) days (empirical distribution), the generation interval with a mean 4.8 (95% CrI 4.3−5.41) and SD 1.7 (95% CrI 1.0−2.6) days (fitted gamma distribution), and the incubation period with a mean 5.5 (95% CrI 5.1−5.8) and SD 4.9 (95% CrI 4.5−5.3) days (fitted log normal distribution). We quantify the impact of the uncertainty surrounding the serial interval, generation interval, incubation period and time delays, on the subsequent estimation of the reproduction number, when pragmatic and more formal approaches are taken. These estimates place empirical bounds on the estimates of most relevant model parameters and are expected to contribute to modelling COVID-19 transmission.

  🖺 Full Text HTML: Meta-analysis of the SARS-CoV-2 serial interval and the impact of parameter uncertainty on the COVID-19 reproduction number
• The Effect of Gender on COVID-19 Infections and Mortality in Germany: Insights From Age- and Sex-Specific Modelling of Contact Rates, Infections, and Deaths -

  Background: Recent research points towards age- and sex-specific transmission of COVID-19 infections and their outcomes. The effect of sex, however, has been overlooked in past modelling approaches of COVID-19 infections. Aim: The aim of our study is to develop an age- and sex-specific model of COVID-19 transmission and to explore how contact changes effect COVID-19 infection and death rates. Method: We consider a compartment model to establish forecasts of the COVID-19 epidemic, in which the compartments are subdivided into different age groups and genders. Estimated contact patterns, based on other studies, are incorporated to account for age- and sex-specific social behaviour. The model is fitted to real data and used for assessing hypothetical scenarios with regard to lockdown measures. Results: Under current mitigation measures as of mid-August, active COVID-19 cases will double by the end of October 2020. Infection rates will be highest among the young and working ages, but will also rise among the old. Sex ratios reveal higher infection risks among women than men at working ages; the opposite holds true at old age. Death rates in all age groups are twice as high among men as women. Small changes in contact rates at working and young ages may have a considerable effect on infections and mortality at old age, with elderly men being always at higher risk of infection and mortality. Discussion: Our results underline the high importance of the non-pharmaceutical mitigation measures in low-infection phases of the pandemic to prevent that an increase in contact rates leads to higher mortality among the elderly. Gender differences in contact rates, in addition to biological mechanisms related to the immune system, may contribute to sex-specific infection rates and their mortality outcome. To further explore possible pathways, more data on COVID-19 transmission is needed which includes socio-demographic information.

  🖺 Full Text HTML: The Effect of Gender on COVID-19 Infections and Mortality in Germany: Insights From Age- and Sex-Specific Modelling of Contact Rates, Infections, and Deaths
• Modeling the role of clusters and diffusion in the evolution of COVID-19 infections during lock-down -

  Epidemics such as the spreading of the SARS-CoV-2 virus are highly non linear, and therefore difficult to predict. In the present pandemic as time evolves, it appears more and more clearly that a clustered dynamics is a key element of description. This means that the disease rapidly evolves within spatially localized networks, that diffuse and eventually create new clusters. We improve upon the simplest possible compartmental model, the SIR model, by adding an additional compartment associated with the clustered individuals. This sophistication is compatible with more advanced compartmental models and allows, at the lowest level of complexity, to leverage the well-mixedness assumption. The so-obtained SBIR model takes into account the effect of inhomogeneity on epidemic spreading, and compares satisfactorily with results on the pandemic propagation in a number of European countries, during and immediately after lock-down. Especially, the decay exponent of the number of new cases after the first peak of the epidemic is captured without the need to vary the coefficients of the model with time. We show that this decay exponent is directly determined by the diffusion of the ensemble of clustered individuals and can be related to a global reproduction number, that overrides the classical, local reproduction number.

  🖺 Full Text HTML: Modeling the role of clusters and diffusion in the evolution of COVID-19 infections during lock-down

From Clinical Trials

• A Study Evaluating the Efficacy and Safety of CKD-314 in Hospitalized Adult Patients Diagnosed With COVID-19 Pneumonia - Condition:   COVID-19
  Intervention:   Drug: Nafamostat Mesilate
  Sponsor:   Chong Kun Dang Pharmaceutical
  Not yet recruiting

• Phase III Double-blind, Placebo-controlled Study of AZD7442 for Post- Exposure Prophylaxis of COVID-19 in Adults - Condition:   COVID-19
  Interventions:   Drug: AZD7442;   Drug: Placebo
  Sponsors:   AstraZeneca;   QuintilesIMS
  Not yet recruiting

• Phase III Double-blind, Placebo-controlled Study of AZD7442 for Pre-exposure Prophylaxis of COVID-19 in Adult. - Condition:   COVID-19
  Interventions:   Drug: AZD7442;   Drug: Placebo
  Sponsors:   AstraZeneca;   QuintilesIMS
  Not yet recruiting

• Effectiveness and Safety of Rhea Health Tone® as add-on Therapy for COVID-19 in Hospitalized Adults in Indonesia - Condition:   Covid19
  Intervention:   Dietary Supplement: Rhea Health Tone®
  Sponsors:   Universitas Padjadjaran;   PT. Rhea Pharmaceutical Sciences Indonesia;   Prodia Diacro Laboratories P.T.
  Not yet recruiting

• Intravenous Infusion of CAP-1002 in Patients With COVID-19 - Condition:   Covid19
  Interventions:   Biological: CAP-1002;   Biological: Placebo
  Sponsor:   Capricor Inc.
  Recruiting

• Clarithromycin Versus Azithromycin in Treatment of Mild COVID-19 Infection - Condition:   Covid19
  Interventions:   Drug: Clarithromycin 500mg;   Drug: Azithromycin;   Drug: Placebo
  Sponsor:   South Valley University
  Completed

• Efficacy of Probiotics in Reducing Duration and Symptoms of COVID-19 - Condition:   COVID-19
  Interventions:   Dietary Supplement: Probiotics (2 strains 10x10^9 UFC);   Dietary Supplement: Placebo (potato starch and magnesium stearate)
  Sponsors:   Centre de recherche du Centre hospitalier universitaire de Sherbrooke;   Lallemand Health Solutions
  Not yet recruiting

• Fase I Clinical Trial on NK Cells for COVID-19 - Conditions:   Covid19;   Sars-cov 2
  Intervention:   Biological: Natural Killer Cells infusion
  Sponsor:   Hospital de Clinicas de Porto Alegre
  Not yet recruiting

• plasmApuane CoV-2 : Efficacy and Safety of Immune Covid-19 Plasma in Covid-19 Pneumonia in Non ITU Patients - Condition:   Covid-19 Pneumonia
  Intervention:   Biological: immune plasma
  Sponsor:   Azienda USL Toscana Nord Ovest
  Recruiting

• Hydrogen Therapy in Patients With Moderate Covid-19 - Condition:   Covid-19
  Intervention:   Drug: Mixture 3,6% H2 in N2 (96.4%)
  Sponsor:   University Hospital, Grenoble
  Not yet recruiting

• Prevention With Chloroquine in Health Personnel Exposed to Infection With Coronavirus Disease 2019 (COVID-19) (TS-COVID) - Condition:   Covid19
  Intervention:   Drug: Chloroquine
  Sponsor:   Fundacion Clinica Valle del Lili
  Active, not recruiting

• Organization of Pulmonary Rehabilitation of Post-COVID-19 Patient With Sequelae (REHABCOVID) - Condition:   Covid19
  Interventions:   Other: Respiratory rehabilitation program (RR).;   Other: Respiratory tele-rehabilitation program (TRR).
  Sponsor:   Centre Hospitalier Intercommunal de Toulon La Seyne sur Mer
  Not yet recruiting

• Inhaled Heparin for Hospitalised COVID-19 Patients - Condition:   Covid19
  Intervention:   Drug: Unfractionated heparin
  Sponsors:   Australian National University;   Helwan University;   Clinica San Camilo, Argentina
  Recruiting

• Effect of Vitamin D on Hospitalized Adults With COVID-19 Infection - Condition:   Covid19
  Interventions:   Drug: Cholecalciferol;   Other: Placebo
  Sponsors:   University of Liege;   Laboratoires SMB S.A.
  Recruiting

• Efficacy and Safety of Acetyl L-Carnitine in COVID-19 Patients With Mild-to-Moderate Disease - Condition:   Covid19
  Intervention:   Dietary Supplement: Acetyl L-Carnitine
  Sponsor:   Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone Palermo
  Not yet recruiting

From PubMed

• Genetically proxied interleukin-6 receptor inhibition: opposing associations with COVID-19 and pneumonia - No abstract

• Zilucoplan in patients with acute hypoxic respiratory failure due to COVID-19 (ZILU-COV): A structured summary of a study protocol for a randomised controlled trial - OBJECTIVES: Zilucoplan (complement C5 inhibitor) has profound effects on inhibiting acute lung injury post COVID-19, and can promote lung repair mechanisms that lead to improvement in lung oxygenation parameters. The purpose of this study is to investigate the efficacy and safety of Zilucoplan in improving oxygenation and short- and long-term outcome of COVID-19 patients with acute hypoxic respiratory failure.

• Natural Products: A Rich Source of Antiviral Drug Lead Candidates for the Management of COVID-19 - Today, the world is suffering from the pandemic of a novel coronavirus disease (COVID-19), a respiratory illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This pandemic is the third fatal coronavirus outbreak that has already occurred in the 21st century. Even six months after its emergence, hundreds of thousands of people are still being infected with SARS-CoV-2, and thousands of lives are lost every day across the world. No effective therapy has been approved to…

• An updated and comprehensive review of the antiviral potential of essential oils and their chemical constituents with special focus on their mechanism of action against various influenza and coronaviruses - Essential oils and their chemical constituents have been reported with well documented antimicrobial effects against a range of bacterial, fungal and viral pathogens. By definition, essential oils are a complex mixture of volatile organic compounds which are synthesized naturally in different parts of the plant as part of plants secondary metabolism. The chemical composition of the essential oils is dominated by the presence of a range of compounds including phenolics, terpenoids, aldehydes,…

• Pharmacological therapies against COVID-19 : state of the art, between hopes and disappointments - The COVID-19 outbreak has raised numerous attempts of diverse pharmacological interventions to improve the prognosis of the infection, especially among hospitalized patients due to an acute respiratory distress syndrome (ARDS). Initially, these interventions used known medications capable to directly target SARS-CoV-2 by investigating several antiviral therapies already applied with some success in other viral infections. Among them remdesivir appears to be the most promising drug against…

• Direct inhibitory effect on viral entry of influenza A and SARS-CoV-2 viruses by azithromycin - CONCLUSIONS: Overall, our findings demonstrate that AZ can exert broad-spectrum antiviral effects against IAV and SARS-CoV-2, and could be served as a potential clinical anti-SARS-CoV-2 drug in emergency as well as a promising lead compound for the development of next-generation anti-IAV drugs.

• Potential inhibitors of SARS-CoV-2: Recent advances - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) appeared in 2019 and is the causative agent of the new pandemic viral disease COVID-19. The outbreak of COVID-19 infection is affecting the entire world, thus many researchers and scientists are desperately looking for suitable vaccines and treatment options. Indeed, researches to find potential inhibitors of SARS-CoV-2 are mainly focused on targeting virus-host interactions or inhibiting viral assembly. Additionally, drugs and other…

• Gender Disaggregation in COVID-19 and Increased Male Susceptibility - Novel coronavirus disease 2019 (COVID-19) is a growing public health crisis. Despite initial focus on the elderly population with comorbidities, it seems that large studies from the worst affected countries follow a sex-disaggregation pattern. Analysis of available data showed marked variations in reported cases between males and females among different countries with higher mortality in males. At this early stage of the pandemic, medical datasets at the individual level are not available;…

• Remdesivir: A beacon of hope from Ebola virus disease to COVID-19 - Since the emergence of coronavirus disease 2019 (Covid-19), many studies have been performed to characterize severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and find the optimum way to combat this virus. After suggestions and assessments of several therapeutic options, remdesivir (GS-5734), a direct-acting antiviral drug previously tested against Ebola virus disease, was found to be moderately effective and probably safe for inhibiting SARS-CoV-2 replication. Finally, on 1 May 2020,…

• Repurposing FDA-approved drugs for SARS-CoV-2 through an ELISA-based screening for the inhibition of RBD/ACE2 interaction - No abstract

• Coronavirus and Its effect on the respiratory system: Is there any association between pneumonia and immune cells - CONCLUSION: The vaccine should receive further attention and in the long run, antiviral drugs and broad-spectrum vaccines are produced for infectious diseases.

• Crystallographic structure of wild-type SARS-CoV-2 main protease acyl-enzyme intermediate with physiological C-terminal autoprocessing site - Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the pathogen that causes the disease COVID-19, produces replicase polyproteins 1a and 1ab that contain, respectively, 11 or 16 nonstructural proteins (nsp). Nsp5 is the main protease (M^(pro)) responsible for cleavage at eleven positions along these polyproteins, including at its own N- and C-terminal boundaries, representing essential processing events for subsequent viral assembly and maturation. We have determined X-ray…

• Garlic (Allium sativum L.): a potential unique therapeutic food rich in organosulfur and flavonoid compounds to fight with COVID-19 - Coronavirus disease 2019 (COVID-19) is the current major health crisis in the world. A successful strategy to combat the COVID-19 pandemic is the improvement of nutritional pattern. Garlic is one of the most efficient natural antibiotics against the wide spectrum of viruses and bacteria. Organosulfur (e.g., allicin and alliin) and flavonoid (e.g., quercetin) compounds are responsible for immunomodulatory effects of this healthy spice. The viral replication process is accelerated with the main…

• Inhibition of S-protein RBD and hACE2 Interaction for Control of SARSCoV-2 Infection (COVID-19) - CONCLUSION: Inhibition of RBD-hACE2 interaction by different molecular scaffolds can be used as a preferred strategy for control of SARS-CoV-2 infection. Recently, published reports pointed out Lys31, Glu35 and Lys353 on B chain of ACE2 as crucial residues for mimicking and design of novel molecules as inhibitors SARS-CoV-2 attachment to human cells. Moreover, some recently identified RBD-hACE2 interaction inhibitors have also been described with their protein binding pattern and potencies (IC50…

• JAK1 Inhibition Blocks Lethal Immune Hypersensitivity in a Mouse Model of Down Syndrome - Individuals with Down syndrome (DS; trisomy 21) display hyperactivation of interferon (IFN) signaling and chronic inflammation, which could potentially be explained by the extra copy of four IFN receptor (IFNR) genes encoded on chromosome 21. However, the clinical effects of IFN hyperactivity in DS remain undefined. Here, we report that a commonly used mouse model of DS overexpresses IFNR genes and shows hypersensitivity to IFN ligands in diverse immune cell types. When treated repeatedly with a…

From Patent Search

• AN EFFICIENT METHODOLOGY TO MANAGE THE ADMISSIONS IN HOSPITALS DURING THE PANDEMICS SUCH AS COVID 19 -

• SARS-CoV-2 예방을 위한 mRNA기반 항원보강제 혼합물 합성 방법 - 본 발명은 SARS-CoV-2(코로나 바이러스) 예방을 위한 mRNA 항원보강제에 관한 것으로 코로나 바이러스에 대한 백신으로서 상기의 항원에 대한 예방을 목적으로 하고 있다. 아이디어에는 보강제에 해당하는 완전프로인트항원보강제(CFA)와 불완전프로인트항원보강제(IFA), 번역과 안정성의 최적화가 된 mRNA, mRNA 운반체, 양이온성 지질 나노입자(lipid nanoparticles)로 구성되며 기존의 백신에 비해 효율성과 안정성의 측면에서 더 향상된 효과를 가지고 있다.

• Vorrichtung zum Reinigen und/oder Desinfizieren von Objekten -

  Vorrichtung (1) zum Desinfizieren von Objekten mit einer Basiseinheit (2), mit einem Aufnahmebehälter (4) für Wasser, welcher an der Basiseinheit (2) montierbar und von der Basiseinheit demontierbar ist, mit einer Objekthalterung (6) zum Halten und/oder Stützen der Objekte (10), wobei diese Objekthalterung (6) in dem Aufnahmebehälter montierbar ist und mit einer elektrisch betriebenen Reinigungseinrichtung (8), welche in dem Wasser befindliche Objekte zumindest mittelbar reinigt oder desinfiziert, wobei diese Reinigungseinrichtung in der Basiseinheit befindliche Erzeugungsmittel zum Erzeugen einer elektrischen Spannung aufweist sowie einen Plasmagenerator und/oder eine Ultraschallerzeugungseinheit.

• Methods for treating Arenaviridae and Coronaviridae virus infections - Provided are methods for treating Arenaviridae and Coronaviridae virus infections by administering nucleosides and prodrugs thereof, of Formula I:

wherein the ’ position of the nucleoside sugar is substituted. The compounds, compositions, and methods provided are particularly useful for the treatment of Lassa virus and Junin virus infections.

• Atemschutz-Baukastensystem -

  Atemschutz-Baukastensystem, das aufweist:

• eine auf zumindest Mund und Nase einer Person aufsetzbare Maske (1), die einen Eingang (11) und einen Ausgang (12) aufweist, und
• mindestens einen Schlauch (3, 31, 32),
• wobei sämtliche Komponenten des Atemschutz-Baukastensystems modular ausgebildet und über Steckverbindungen oder Schraubverbindungen (115, 125, 155, 165, 175, 215, 315, 75, 915) miteinander verbindbar sind, um der Maske (1) Luft über deren Eingang (11) zuzuführen und/oder ausgeatmete Luft vom Ausgang (12) der Maske (1) wegzuführen.

• Vorrichtung zur Übergabe und Dekontamination von mit Krankheitserregern kontaminierten Gegenständen oder Erzeugnissen -

  Vorrichtung zur Übergabe von mit Krankheitserregern kontaminierten Gegenständen oder Erzeugnissen nach einer Dekontamination, umfassend eine Einrichtung zur Dekontamination der mit Krankheitserregern kontaminierten Gegenstände oder Erzeugnisse mit mindestens einer UV-Strahlungsquelle (24), eine Durchzugseinrichtung mit Ein- und/oder Ausgabebereichen für die kontaminierten bzw. dekontaminierten Gegenstände oder Erzeugnisse, dadurch gekennzeichnet, dass die Durchzugseinrichtung im Eingang bzw. im Ausgang zum Ein- und/oder Ausgabebereich angeordnete sich paarweise gegenüberliegende Walzen (17) und Räder (4) umfasst, die zum Einzug bzw. zur Ausgabe der kontaminierten bzw. dekontaminierten Gegenstände oder Erzeugnisse vorgesehen sind, wobei die Walzen (17) und die Räder (4) durch im Ein- und/oder Ausgabebereich angeordnete Sensoren (23) und einer elektronische Kontrolleinheit (27) in Bewegung bringbar sind, wobei die Gegenstände oder Erzeugnisse in den Bereich der Einrichtung zur Dekontamination förderbar sind, der zwischen den paarweise angeordneten Walzen (17) und Rädern (4) vorgesehen ist, welcher sich gegenüberliegende Platten (25) aus Quarzglas oder einem UV-transparenten Polymermaterial, wie Graphen oder Kunstglas umfasst, über bzw. unter welchen die UV-Strahlungsquelle (24) angeordnet ist, welche als UVC-LED-Leiste und/oder Modul mit mindestens einer LED-Lampe ausgebildet ist.

• 제2형 중증급성호흡기증후군 코로나바이러스 감염 질환의 예방 또는 치료용 조성물 - 본 발명은 화학식 1로 표시되는 화합물, 또는 이의 약학적으로 허용가능한 염을 유효성분으로 포함하는 제2형 중증급성호흡기증후군 코로나바이러스 감염 질환 예방 또는 치료용 약학적 조성물을 제공한다. [화학식 1] .

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• 新型冠状病毒中和性抗体滴度检测ELISA试剂盒 - 本发明提供一种新型冠状病毒中和性抗体滴度检测ELISA试剂盒，其中包括：包被有生物素‑链霉亲和素标记的人ACE2蛋白的酶标板、辣根过氧化酶标记的新型冠状病毒RBD蛋白、新型冠状病毒中和性抗体阳性对照、包被液、洗涤液、稀释液、封闭液、显色液和终止液等。该试剂盒具有成本低，操作简单，高灵敏度、高特异性、高准确度的特点，可用于新型冠状病毒中和抗体的批量、快速检测。

• Reagenzien und Verwendungen zur Diagnose einer SARS-CoV-2-Infektion -

  Diagnostisch nützlicher Träger umfassend ein Polypeptid umfassend SEQ ID NO1 oder eine Variante davon, die an einen Antikörper gegen SEQ ID NO1 aus einer Probe von einem Patienten binden kann, der an einer SARS-CoV-2-Infektion leidet, wobei das Polypeptid bevorzugt auf der Festphase des Trägers immobilisiert ist.

• Reagenzien und Verwendungen zur Diagnose einer SARS-CoV-2-Infektion -

  Verwendung eines Polypeptides umfassend SEQ ID NO1 oder eine Variante davon, die an einen Antikörper gegen SED ID NO1 aus einer Probe von einem Patienten binden kann, zur Herstellung eines diagnostischen Kits.